P529: FIRST EUROPEAN REAL-WORLD EVIDENCE PROSPECTIVE REGISTRY OF FIRST-LINE ADULT PATIENTS WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM TREATED WITH FIRST-IN-CLASS CD123-TARGETED THERAPY TAGRAXOFUSP
Authors: U. Platzbecker, E. Angelucci, P. Montesinos, R. M. Lemoli, A. Spyridonidis, J. Casariego, T. I. Mughal, M. Mohty
Journal: HemaSphere (2022)

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy derived from plasmacytoid dendritic cells that overexpress interleukin-3 (IL-3) receptor alpha (CD123). It is a highly aggressive disease characterized by skin and bone marrow involvement and is associated with a poor prognosis (median overall survival 8–14 months). Tagraxofusp (TAG, SL-401) is a first-in-class CD123-targeted therapy comprising human IL-3 fused to a truncated diphtheria toxin payload. It is currently the only approved first-line (1L) treatment for adult patients (pts) with BPDCN in Europe. As of July 2021, 65 pts with BPDCN have received TAG in a clinical setting outside the US as part of an expanded access program. Collecting real-world clinical data from TAG is important to increase understanding of clinical outcomes, especially in pts commonly underrepresented in clinical trials. We describe the first real-world evidence prospective registry in pts with BPDCN receiving TAG. It has been designed to meet requirements outlined in the marketing authorization of the European Commission for further evaluation of the efficacy and safety of TAG in pts with 1L or relapsed/refractory BPDCN. Aims: To investigate effectiveness and safety of TAG in pts with 1L BPDCN. Methods: This is a noninterventional, single-arm, post-authorization study (EudraCT: 2021-001684-24) in adult pts with BPDCN prescribed TAG under real-world routine clinical practice conditions (12 mcg/kg intravenously [IV] once daily on days 1–5 of a 21-day cycle, per the summary of product characteristics recommendation). A minimum of 80 pts will be included in approximately 40–55 sites in Europe, estimated over 4 years. Eligible pts have a diagnosis of BPDCN and are to be treated (or have recently started treatment) with TAG monotherapy as 1L treatment, per physician’s decision. Primary endpoints are rate of complete response (CR), defined as CR + clinical CR (CR with residual skin abnormality not indicative of active disease) after 3 months of treatment, and safety of TAG including the incidence and severity of capillary leak syndrome (CLS). Secondary endpoints include number of pts bridging to SCT, progression-free survival, overall survival, best overall response, duration of response, TAG dose interruptions/administration of IV albumin supplementation in pts with CLS or CLS symptoms, as well as safety and incidence and severity of adverse events of special interest (which include CLS and hepatic, renal, and cardiac events). Quarterly data collection is anticipated, as well as collection at screening, enrollment, early discontinuation, and study end (Figure). Safety data collection will end 18 months after the last enrolled pt’s first visit (LPFV). Interim analyses will be performed annually; an effectiveness interim analysis is scheduled at 20 months post-LPFV. Analyses will be performed using descriptive statistics. Survival data will be summarized using the Kaplan-Meier method. Subgroup analyses for effectiveness and safety may be performed, on the basis of gender, age, or baseline Eastern Cooperative Oncology Group performance status. Enrollment is planned to start by June 2022. Taking the registry as the basis, upon study finalization a complementary comparative analysis of effectiveness and safety data from the TAG registry with a retrospective clinical cohort will be undertaken using appropriate methodology, such as propensity score matching or inverse probability treatment weighting. Results: This is a TiP and there are no results at this time. Image:Summary/Conclusion: This is a TiP and there are no results at this time.